Recent observations from retrospective cohort studies indicate that HIV-associated TB is associated with reduced survival and increased rate of opportunistic infections compared to CD4-matched controls. Mounting evidence from immunologic and virologic studies, in fact, supports the concept of co-pathogenesis in which cytokines such as tumor necrosis factor alpha (TNF) are over-expressed during the course of TB and stimulate viral replication in latently infected cells, possibly leading to greater viral load. The results of recent Phase I/II trials in HIV/TB of selective cytokine inhibitors, such as thalidomide and pentoxifylline, indicate short-term clinical benefit and reduced viral load, despite the only partial inhibition of TNF achieved by either agent. Because TB is associated with increased expression of multiple cytokines, a less selective agent than thalidomide and a more potent agent than pentoxifylline may be more effective. Attractive alternatives to the more selective inhibitors are the glucocorticoids because they are potent inhibitors of cytokines, including TNF, and because clinicians have extensive experiences with their use in HIV infection. Although corticosteroid use in HIV infection has a record of safety, the safety and bioavailability of corticosteroids in HIV/TB has not been established. The Investigator, therefore, proposes two interrelated studies with the following specific objectives: (1) to determine the dose of oral prednisolone that provides optimal therapeutic activity, as measured by reduction in induced TNF ex vivo, and is safe as adjuvant therapy for smear-positive pulmonary TB in HIV -infected Ugandan adults; (2) to evaluate the biologic activity, as the change in viral load and CD4 count, of oral prednisolone in this population. To address these objectives, the Investigator and his associates will perform a Phase I, pharmokinetic study to identify the optimal dose of oral prednisolone and a Phase II study to confirm the safety of prednisolone and evaluate its biologic activity. The proposed trial will be conducted in a developing country setting because prednisolone is an affordable and available intervention which, if found safe and effective, could have substantial impact on the morbidity of HIV-associated TB.